Increased atherogenic low-density lipoprotein cholesterol in untreated subclinical hypothyroidism

To evaluate the effects of physiologic doses of levothyroxine replacement on the lipoprotein profile in patients with subclinical hypothyroidism (SCH).

In a prospective, double-blind, placebo-controlled study, we enrolled 120 patients--mostly, but not exclusively, premenopausal women--with SCH. Patients were randomly assigned to either a levothyroxine-treated group (n = 60) or a placebo (control) group (n = 60). Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) were measured before and 52 weeks after assignment to either group.

In the levothyroxine-treated group, the lipoprotein mean values before and after the 52-week study were as follows: TC, 5.05 +/- 0.98 mmol/L versus 4.74 +/- 0.87 mmol/L (P<.0001); LDL-C, 3.30 +/- 0.90 mmol/L versus 2.89 +/- 0.59 mmol/L (P<.01); TG, 1.18 +/- 0.71 mmol/L versus 0.95 +/- 0.53 mmol/L (P<.002); and HDL-C, 1.20 +/- 0.33 mmol/L versus 1.19 +/- 0.32 mmol/L (P = .29). In the control group, TC, HDL-C, and TG values remained unchanged after 52 weeks in comparison with baseline, but LDL-C mean values increased from 2.79 +/- 0.60 mmol/L to 3.11 +/- 0.77 mmol/L, a change that was statistically significant (P<.001). At the end of the study, the lipid profile changes between levothyroxine-treated and control groups were compared. Total cholesterol and LDL-C were significantly lower in the levothyroxine-receiving group (P<.029 and P<.0001, respectively) in comparison with the control group. The difference did not reach statistical significance for TG and HDL-C values.

In premenopausal women, SCH has a negative effect on the lipoprotein profile and may translate into a sizable cardiovascular risk if left untreated.